Staff View: Genetic Regulation of the yefM-yoeBSpn Toxin-Antitoxin Locus of Streptococcus pneumoniae

Genetic Regulation of the yefM-yoeBSpn Toxin-Antitoxin Locus of Streptococcus pneumoniae

Type II (proteic) toxin-antitoxin systems (TAS) are ubiquitous among bacteria. In the chromosome of the pathogenic bacterium Streptococcus pneumoniae there are at least eight putative TAS, one of them being the yefM-yoeB(Spn) operon studied here. Through footprinting analyses, we showed that purifie...

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Main Authors:	Chan, W.T., Nieto, C., Harikrishna, J.A., Khoo, S.K., Yasmin Othman, R., Espinosa, M., Yeo, C.C.
Format:	Article
Published:	American Society for Microbiology 2011
Subjects:	R Medicine
Online Access:	http://eprints.um.edu.my/1907/ http://www.ncbi.nlm.nih.gov/pubmed/21764929
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spelling	my.um.eprints.19072013-12-11T06:54:44Z http://eprints.um.edu.my/1907/ Genetic Regulation of the yefM-yoeBSpn Toxin-Antitoxin Locus of Streptococcus pneumoniae Chan, W.T. Nieto, C. Harikrishna, J.A. Khoo, S.K. Yasmin Othman, R. Espinosa, M. Yeo, C.C. R Medicine Type II (proteic) toxin-antitoxin systems (TAS) are ubiquitous among bacteria. In the chromosome of the pathogenic bacterium Streptococcus pneumoniae there are at least eight putative TAS, one of them being the yefM-yoeB(Spn) operon studied here. Through footprinting analyses, we showed that purified YefM(Spn) antitoxin and the YefM-YoeB(Spn) TA protein complex bind to a palindrome sequence encompassing the -35 region of the main promoter (P(yefM2)) of the operon. Thus, the locus appeared to be negatively autoregulated with respect to P(yefM2) as YefM(Spn) behaved as a weak repressor with YoeB(Spn) as a co-repressor. Interestingly, a BOX element, composed of a single copy each of boxA and boxC sub-elements was found upstream of promoter P(yefM2). BOX sequences are pneumococcal, perhaps mobile, genetic elements that have been associated with bacterial processes such as phase variation, virulence regulation and genetic competence. In the yefM-yoeB(Spn) locus, the boxAC element provided an additional weak promoter, P(yefM1), upstream of P(yefM2) which was not regulated by the TA proteins. In addition, transcriptional fusions with a lacZ reporter gene showed that P(yefM1) was constitutive albeit weaker than P(yefM2). Intriguingly, the coupling of the boxAC element to P(yefM1) and yefM(Spn) in cis (but not in trans) led to transcriptional activation indicating that the regulation of the yefM-yoeB(Spn) locus differ somewhat from other TA loci and may involve as-yet unidentified elements. Conservation of the boxAC sequences in all available sequenced genomes of S. pneumoniae which contained the yefM-yoeB(Spn) locus suggested that its presence may provide a selective advantage to the bacterium. American Society for Microbiology 2011 Article PeerReviewed Chan, W.T. and Nieto, C. and Harikrishna, J.A. and Khoo, S.K. and Yasmin Othman, R. and Espinosa, M. and Yeo, C.C. (2011) Genetic Regulation of the yefM-yoeBSpn Toxin-Antitoxin Locus of Streptococcus pneumoniae. Journal of Bacteriology. ISSN 0021-9193 http://www.ncbi.nlm.nih.gov/pubmed/21764929 21764929
institution	Universiti Malaya
building	UM Library
collection	Institutional Repository
continent	Asia
country	Malaysia
content_provider	Universiti Malaya
content_source	UM Research Repository
url_provider	http://eprints.um.edu.my/
topic	R Medicine
spellingShingle	R Medicine Chan, W.T. Nieto, C. Harikrishna, J.A. Khoo, S.K. Yasmin Othman, R. Espinosa, M. Yeo, C.C. Genetic Regulation of the yefM-yoeBSpn Toxin-Antitoxin Locus of Streptococcus pneumoniae
description	Type II (proteic) toxin-antitoxin systems (TAS) are ubiquitous among bacteria. In the chromosome of the pathogenic bacterium Streptococcus pneumoniae there are at least eight putative TAS, one of them being the yefM-yoeB(Spn) operon studied here. Through footprinting analyses, we showed that purified YefM(Spn) antitoxin and the YefM-YoeB(Spn) TA protein complex bind to a palindrome sequence encompassing the -35 region of the main promoter (P(yefM2)) of the operon. Thus, the locus appeared to be negatively autoregulated with respect to P(yefM2) as YefM(Spn) behaved as a weak repressor with YoeB(Spn) as a co-repressor. Interestingly, a BOX element, composed of a single copy each of boxA and boxC sub-elements was found upstream of promoter P(yefM2). BOX sequences are pneumococcal, perhaps mobile, genetic elements that have been associated with bacterial processes such as phase variation, virulence regulation and genetic competence. In the yefM-yoeB(Spn) locus, the boxAC element provided an additional weak promoter, P(yefM1), upstream of P(yefM2) which was not regulated by the TA proteins. In addition, transcriptional fusions with a lacZ reporter gene showed that P(yefM1) was constitutive albeit weaker than P(yefM2). Intriguingly, the coupling of the boxAC element to P(yefM1) and yefM(Spn) in cis (but not in trans) led to transcriptional activation indicating that the regulation of the yefM-yoeB(Spn) locus differ somewhat from other TA loci and may involve as-yet unidentified elements. Conservation of the boxAC sequences in all available sequenced genomes of S. pneumoniae which contained the yefM-yoeB(Spn) locus suggested that its presence may provide a selective advantage to the bacterium.
format	Article
author	Chan, W.T. Nieto, C. Harikrishna, J.A. Khoo, S.K. Yasmin Othman, R. Espinosa, M. Yeo, C.C.
author_facet	Chan, W.T. Nieto, C. Harikrishna, J.A. Khoo, S.K. Yasmin Othman, R. Espinosa, M. Yeo, C.C.
author_sort	Chan, W.T.
title	Genetic Regulation of the yefM-yoeBSpn Toxin-Antitoxin Locus of Streptococcus pneumoniae
title_short	Genetic Regulation of the yefM-yoeBSpn Toxin-Antitoxin Locus of Streptococcus pneumoniae
title_full	Genetic Regulation of the yefM-yoeBSpn Toxin-Antitoxin Locus of Streptococcus pneumoniae
title_fullStr	Genetic Regulation of the yefM-yoeBSpn Toxin-Antitoxin Locus of Streptococcus pneumoniae
title_full_unstemmed	Genetic Regulation of the yefM-yoeBSpn Toxin-Antitoxin Locus of Streptococcus pneumoniae
title_sort	genetic regulation of the yefm-yoebspn toxin-antitoxin locus of streptococcus pneumoniae
publisher	American Society for Microbiology
publishDate	2011
url	http://eprints.um.edu.my/1907/ http://www.ncbi.nlm.nih.gov/pubmed/21764929
_version_	1643686792249999360
score	13.211869

Genetic Regulation of the yefM-yoeBSpn Toxin-Antitoxin Locus of Streptococcus pneumoniae

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